Thyroid Autoimmunity, Leaky Gut Syndrome, and the 4R Protocol

I’ve discussed leaky gut syndrome in the past, as this is commonly associated with conditions such as Graves’ Disease and Hashimoto’s Thyroiditis. In fact, some researchers believe that ALL autoimmune conditions are associated with an increase in intestinal permeability (a leaky gut). I’m not sure if I agree with this, as while I don’t test every single one of my patients for a leaky gut, of those people I have tested for this who have elevated autoantibodies, a few of them have come back with negative results. In any case, if it is determined that someone has a leaky gut then you want to consider implementing the 4R protocol.

But what is the 4R protocol? Before talking about this I would briefly like to remind everyone reading this what happens when someone has a leaky gut. In a normal, healthy gut, the cells of the intestines (enterocytes) should be held close together by tight junctions. Tight junctions regulate the permeability of ions, macro molecules, and cells via the paracellular pathway (1). In other words, these tight junctions prevent larger molecules and other substances from passing between the cells of the intestine.

However, certain factors can break down these tight junctions, and thus lead to what’s referred to as an “increase in intestinal permeability”. An “increase in intestinal permeability” is synonymous with a “leaky gut”. So disruption of these tight junctions leads to an inadequate epithelial barrier, and this in turn results in an incontrollable water and electrolyte loss, and is implicated in the pathogenesis of numerous autoimmune and inflammatory diseases (1).

In the past I’ve discussed the intestinal permeability test from Cyrex Labs, which can measure the antibodies against these tight junction proteins. Occludin and zonulin are two tight junction proteins. Occludin is part of the main component of proteins which hold together the tight junctions, while zonulin is a protein which regulates the permeability of the intestine (2). When someone has a leaky gut, there will be elevated antibodies to both occludin and zonulin, and this is what the test from Cyrex Labs measures. This test also detects antibodies against actomyosin, which helps to regulate intestinal barrier function.

Hopefully you now have a better understanding of what a leaky gut entails. Now let’s take a look at what the 4R protocol involves:

1. Remove. First of all, you want to remove the factor or factors which caused the increase in intestinal permeability. So for example, gluten is a common factor which can lead to an increase in intestinal permeability. However, there can be other factors which can cause a leaky gut to occur. In addition to gluten, other food allergens can be a factor. Certain pathogens can also compromise the tight junctions, thus causing an increase in intestinal permeability. Unfortunately stress can also be a factor, as high cortisol levels can lead to a decreased secretory IgA, making someone more susceptible to developing a leaky gut. Certain medications such as NSAIDs can also cause a leaky gut.

Sometimes it admittedly can be a challenge to determine what is causing the increase in intestinal permeability. Although it’s easy enough to avoid gluten and dairy, what if another food is responsible for the leaky gut? There are many different types of pathogens, and so how can one determine if a specific pathogen is the culprit? Everyone deals with stress, and so how do you know if this is the trigger? Some detective work is usually required, which is one reason why it’s not recommended to self treat your condition. Although finding the trigger under the guidance of a natural healthcare professional can still be challenging, in my opinion it still is best to work with someone who has the knowledge and experience dealing with these conditions.

After removing the factor or factors which caused the leaky gut, you want to focus on the next 3 components of the 4R protocol:

2. Replace. You want to replace those factors which are necessary for proper digestion. Some examples include digestive enzymes, betaine HCL, and dietary fiber. I frequently give digestive enzymes to my patients and recommend for them to consume enough dietary fiber. As for betaine HCL, whether someone should take this or not depends on the patient. The goal isn’t for the person to take digestive enzymes and/or betaine HCL on a permanent basis, but many times it is a good idea for patients to take these while following a natural treatment protocol to make sure they’re digesting the food they’re eating and the nutrients from the supplements they’re taking.

3. Reinoculate. This is where prebiotics and probiotics come into play. Remember that the probiotic strain does make a big difference. For example, bifidobacterium lactis HN019 is great for intestinal dysbiosis, while Saccharomyces boulardii can help with a yeast infection and play a role in gut repair. Prebiotics such as inulin can help to enhance the growth of the beneficial bacteria. For more information on probiotics I recommend checking out my article entitled “Can Taking Probiotics Improve Thyroid Health?“.

4. Repair. It of course is important to repair the gut. L-glutamine is an amino acid, and this is one of the best nutrients used for gut repair. When I’m working with someone who has a leaky gut I’ll commonly recommend at least 5,000 mg of L-glutamine per day, and with some people I’ll recommend higher doses. I mentioned before that Saccharomyces boulardii can help with gut repair. Certain herbs can help with the mucosal lining such as slippery elm, marshmallow root, and aloe vera. Zinc can also be beneficial. However, certain foods can help with the healing of the gut as well, including bone broth, cabbage juice, and fermented foods such as sauerkraut and kimchi.

In the opening paragraph of this post I discussed how some researchers hypothesize that in addition to genetic and environmental factors, loss of intestinal barrier function (a leaky gut) is necessary to develop autoimmunity (3). However, these same researchers also feel that once the autoimmune process is activated, it is not auto-perpetuating, but rather can be modulated or even reversed by preventing the continuous interplay between genes and environment (3). In other words, not only can a leaky gut be cured, but the autoimmune process can be modulated and in many cases even reversed.

I’ve been mentioning this for many years due to my personal experience with Graves’ Disease, along with the experiences of many of my patients with autoimmune thyroid conditions. But even though the research shows that the autoimmune process can be modulated, most medical doctors don’t do anything to address the autoimmune component of Graves’ Disease and Hashimoto’s Thyroiditis, as they just focus on managing the thyroid symptoms. This doesn’t mean that addressing autoimmunity is an easy process, as it can be a challenge finding out what the trigger is. And if someone has a condition such as leaky gut syndrome it can take a good amount of time to correct the problem. But in most cases it is worth the “hassle”, especially when compared to receiving radioactive iodine and/or having to take thyroid hormone medication for the rest of your life.

In summary, leaky gut syndrome is common in autoimmune conditions such as Graves’ Disease and Hashimoto’s Thyroiditis. And when dealing with a leaky gut, one wants to implement the 4R protocol. Doing so not only can help to correct the leaky gut, but if this is what’s responsible for one’s autoimmune condition then it can be the key factor in restoring their overall health back to normal.

This depends on the person, as some people will notice an improvement in their symptoms after a few weeks, while for others it might take one or two months. As for how long it takes to completely heal the gut, this also depends on the person, as well as the severity of the leaky gut, as in most cases it will take at least 3 to 6 months, but for some people it can take one year or longer to completely heal the gut.